Lysosomal storage disorder (LSDs) are a large family of genetic disorders that can lead to the manifestation of severe clinical symptoms. Although the frequency of each individual disease is relatively rare, the collective incidence of all lysosomal storage disorders is about 1 in 7000 newborns. This is greater than that of other diseases, such as phenylketonuria, for which newborn screening methods are available. Each lysosomal storage disorder results from a deficiency in a lysosomal enzyme, transporter or protein involved in lysosomal biogenesis or function [1]. The deficiency leads to the accumulation of substrates, normally degraded within the lysosome, and an increase in size and number of lysosomes within the cells.
Predominantly affecting young children, LSDs can be very severe with a wide range of clinical symptoms that depend on the particular genotype involved including mental retardation, skeletal abnormalities, organomegaly, corneal clouding and coarse facial features [2] [1]. In recent years treatments for several LSDs have become possible including drug therapy [3-5], bone marrow transplantation [2, 6], and enzyme replacement therapy [6, 7]. New treatment protocols are being developed with the increased knowledge of the underlying cause of the specific disorders, and the availability of animal models together with the development of new technologies. Animal models are of particular importance for the testing of new treatments such as enzyme replacement therapy [2, 6, 8, 9], and studies in animal models have also shown that maximum efficacy, in most cases, is achieved when treatment is given at an early stage of pathology [10, 11].
In most of the disorders, clinical pathology is not apparent at birth but presents in the first few years of life. For current and proposed therapies to achieve maximum efficacy it is important that the disorders are detected early, before the onset of irreversible pathology, particularly if there is central nervous system and/or bone pathology involvement. Thus, there is a need for screening methods for newborns, preferably screening methods that can detect all or most lysosomal disorders with a minimum number of assays. The present invention fulfils this and other needs.